The role of nicotine titration in tobacco dependence will be studied. Special attention will be given to comparisons of adolescent and adult tobacco smokers. In particular, the importance of puffing and inhaling patterns in the regulation of nicotine delivery to smokers will be evaluated. The specific aims are: (1) to determine the relative contribution of smoking patterns and metabolic factors on postsmoking blood levels; (2) to investigate how the same smoker obtains either the excitatory or relaxing effects of nicotine by altering puffing and inhalation patterns, and (3) to clarify the role of nicotine in stress induced smoking. Puff volume will be measured by a flow meter and inhalation volume will be measured by inductance pneumography. The use of both techniques provides a noninvasive and precise profile of how each cigarette is smoked on a puff by puff basis. Blood samples will be assayed for nicotine and cotinine by gas chromatographic methods. These studies are motivated by observations that nicotine blood levels are very similar for smokers of cigarettes with low and high machine nicotine deliveries. Thus, smokers have greater control over their nicotine dose than previously was thought. This control is exercised with subtle manipulations of puffing and inhalation patterns. Methods involve several disciplines including psychopharmacology, psycho-physiology, respiratory physiology, pharmacokinetics and behavioral medicine. The studies have direct public health implications since they challenge the notion of a safe cigarette and emphasize the smokers' role in determining their own exposure to nicotine and combustion products. A detailed examination of smoking behavior in adolescent smokers may enhance prevention strategies.